This program is designed to examine several factors which affect growth and specialized function in cultured mammalian cells. Dispersed cell cultures derived from functional malignant tumors and from analogous nonmalignant normal tissues will be established. Organ- specific function, for example, the biosynthesis and secretion of ACTH or growth hormone by cell cultures derived from the pituitary gland, or of parathyroid hormone or thyrocalcitonin by cell cultures of the parathyroid and thyroid glands, respectively, will be measured by immunological and biological assay methods. Nutrients required for cell growth and for cell function will be determined and compared. Attempts will be made to clone the functional cells and to determine their karyotype. The effects of factors which are known to control the metabolic activity of these cells in vivo (such as hypothalamic polypeptides which stimulate or inhibit the release of specific hormones from the pituitary gland, or of calcium ion concentrations which affect the secretion of parathyroid hormone or thyrocalcitonin) will be examined in vitro. These studies may enhance knowledge of the manner in which these factors act on target cells. Conversely, comparison of the established effects of these agents in the whole animal to their effects on cultured cells may allow new inferences about the relevance and validity of in vitro findings to normal physiological processes.